1. Field of the Invention
The present invention relates to the use of an opioid antagonist such as naltrexone in combination with one or more serotonin (5-hydroxytryptamine or 5-HT) or norepinephrine reuptake inhibitor(s) and/or lithium to treat mental or emotional disorders characterized by depression, obsessiveness, depression with anxiety, mania, manic depression, depression with manic episodes, and depression concomitant with an illness causing seizures which are inhibited by carbamazepine, or a combination of any of these mental or emotional illnesses, or mental or emotional illnesses with seizures. The inventor has discovered that naltrexone is useful in combination with lithium and/or one or more serotonin (5-HT) uptake inhibitor and/or norepinephrine (N.E.) uptake inhibitor drug compounds in treating patients whose depression and/or associated mental illnesses or conditions were refractory to drug treatment using one or more known antidepressant agents or agents for manic and manic depressive disorders such as lithium, and tricyclic and a-typical antidepressants including, but not limited to clomipramine, amitriptyline, imipramine, sertraline and nortriptyline that inhibit 5-HT and/or N.E. reuptake.
The inventor has further discovered that such treatment using naltrexone in combination with lithium and/or 5-HT or N.E. reuptake inhibitors is effective even where benzodiazepines are concurrently administered to treat anxiety. Additionally, the inventor has discovered that lithium in combination with naltrexone in some cases reduces manic and manic depressive bipolar symptoms.
2. Description of the Related Prior Art
A general discussion of the effectiveness of tricyclic antidepressants and non-tricyclic a-typical antidepressants in inhibiting 5-HT and/or N.E. neuronal synaptic reuptake and in treating depression, along with the pharmacology of these compounds is found in Goodman and Gillman, The Pharmacological Basis of Therapeutics, 7th and 8th Eds. (MacMillan Publ. Co.) Chapt. 19, Section 11 "Drugs Used in the Treatment of Disorders of Mood", incorporated by reference herein. According to the present invention, tricyclic antidepressants include, but are not limited to, imipramine, amitriptyline, trimipramine, doxepin, desipramine, nortriptyline, protriptyline, amoxapine, clomipramine, maprotriline, and carbamazepine, and their pharmaceutically effective salts and esters, such as, but not limited to their hydrochlorides, maleates, tartrates and lactates. Although carbamazepine is approved in the U.S. as antiepileptic, it is chemically related to tricyclic antidepressants, its actions on human brain neurons are not completely known, and for the present invention it is classified as a tricyclic antidepressant. See, Goodman and Gillman, The Pharmacological Basis of Therapeutics, referenced above, 7th Ed., page 457 et seq.
According to the present invention, a-typical antidepressants include, but are not limited to, bupropion, sertraline, fluoxetine, and trazodone and their pharmacologically effective salts and esters, such as, but not limited to, their hydrochlorides, maleates, tartrates and lactates.
Additional discussion of these drug compounds and their analogs' pharmacologic action in inhibiting 5-HT and N.E. and in treating depression is found in the Physician's Desk Reference (PDR), 47th Ed., 1993, published by Medical Economics Co., Inc., Montvale, N.J., indexed by generic compound name and incorporated by reference herein.
The opioid antagonists which may be employed in the present invention have been known for use in treatment of opioid overdose and to prevent abuse of opioids such as heroin or morphine. The pharmacology of opioid antagonist compounds are described in Goodman and Gillman, Pharmacological Basis of Therapeutics, 7th & 8th Eds. (as noted above), Chapt. 22, "Opioid Antagonists", incorporated by reference herein, and include, but are not limited to cyclazocine, naloxone, opioid antagonist compounds having the same pentacyclic nucleus as nalmefene, naltrexone, nalmefene, nalorphine, nalbuphine, thebaine, levallorphan, pentazocine, oxymorphone, butorphanol, buprenorphine, levorphanol, meptazinol, dezocine, and pentazocine and their pharmacologically effective salts and esters such as, but not limited to their hydrochlorides, maleates, tartrates and lactates.
The generally accepted use for opioid antagonists in treatment of human ailments has been for reversing opioid toxicity and overdoes, and in preventing abuse of opioids, such as heroin and morphine. However, Glover, in U.S. Pat. No. 5,028,612 incorporated by reference herein, discusses use of opioid antagonists, such as naltrexone, in a method for treating emotional numbness where emotional numbness is "conceptualized as a biopsychological response to extreme emotional or physical trauma" and is featured by a person's subjective experience of inability to feel emotions, and lack of care and concern for others.
Glover also discloses that naltrexone may be used in treatment of emotional numbness coupled with other emotional disorders, such as post traumatic stress syndrome, schizophrenia, depression, anxiety, hypochondria, and psychomotor disorders, although no support for success in treating such patients is disclosed.
Horrobin in U.S. Pat. No. 4,388,324 discloses a method of moderating the effects of taking alcohol by administering, among other compositions, a composition of .gamma.-linolenic acid and/or ascorbic acid and/or ethyl alcohol and/or opioid antagonist (See, col. 7, lines 30-35). Horrobin discloses that endogenous opioid excess, suspected in schizophrenia, coeliac diseases and psoriasis may be reversed by opioid antagonists such as naloxone (See, U.S. Pat. No. 4,388,32, col. 3, lines 15-19).